Ignet

Gene Pair Information

Gene Pair: INS, IRS1

Related Sentences

#	PMID	Sentence
1	1380456	IRS-1 undergoes rapid tyrosine phosphorylation during insulin stimulation and forms a stable complex containing the 85 kDa subunit (p85) of the phosphatidylinositol (PtdIns) 3'-kinase, but p85 is not tyrosyl phosphorylated.
2	1380456	Furthermore, overexpression of IRS-1 potentiates the activation of PtdIns 3-kinase in insulin-stimulated cells, and tyrosyl phosphorylated IRS-1 or peptides containing phosphorylated YXXM motifs activate PtdIns 3'-kinase in vitro.
3	1380456	We conclude that the binding of tyrosyl phosphorylated IRS-1 to the SH2 domains of p85 is the critical step that activates PtdIns 3'-kinase during insulin stimulation.
4	1385403	Insulin immediately stimulated tyrosine phosphorylation of IRS-1, and after 10-30 min with insulin its apparent molecular mass increased to 175-180 kDa.
5	1385403	Purified insulin receptors directly phosphorylated baculovirus-produced IRS-1 exclusively on tyrosine residues.
6	1385403	In addition, a phosphatidylinositol 3'-kinase associated with IRS-1 during insulin stimulation, and this association was more sensitive to insulin in CHO cells overexpressing the insulin receptor (CHO/IR cells), more responsive to insulin to CHO/IRS-1 cells, and both sensitive and responsive in CHO/IR/IRS-1 cells.
7	7504175	These results extend the notion that IRS-1 is a multisite docking protein that engages various downstream regulatory elements during insulin signal transmission.
8	8196603	Interestingly, IRS-1, but not IRS-1F-895, enhanced the stimulation of MAP kinase by insulin in 32-D cells expressing insulin receptors.
9	7520127	Chronic insulin treatment also produced a 30% decrease in PI 3-kinase protein levels and a approximately 50% decrease in the association/activation between IRS-1/PI 3-kinase.
10	8049217	However, they fail to undergo insulin-stimulated internalization, do not regulate the phosphorylation of insulin receptor substrate 1, and are unable to mediate an insulin-stimulated increase in DNA synthesis and c-jun and c-fos expression.
11	7895862	The regulation of IRS-1 has been analyzed in animal models of insulin resistance, and its mechanism has been studied in culture cells.
12	7895862	In cultured cell such as 3T3-L1 or 3T3-F442A adipocytes, IRS-1 was negatively regulated both by insulin and dexamethasone by different mechanisms.
13	7895862	Insulin regulates the IRS-1 expression at protein level mainly by decreasing the half life of IRS-1 protein, and dexamethasone regulates it at mRNA level mainly by decreasing the half life of IRS-1 mRNA.
14	7486683	In HIR 3.5 cells, which contain similar numbers of PDGF and insulin receptors, insulin, but not PDGF, stimulated tyrosyl phosphorylation of IRS-1.
15	7486683	Thus, the insulin signal differs from that of PDGF by the insertion of a cytosolic, nonreceptor SH2 domain docking protein (IRS-1).
16	8910437	However, Grb2 association with IRS-1 could not be detected in the basal or insulin-stimulated states, and mitogen-activated protein kinase (MAPK) activity could not be stimulated by insulin, epidermal growth factor, or platelet-derived growth factor.
17	9204876	During insulin stimulation, p85 associated with pp60(IRS3) more rapidly than with IRS-1 or IRS-2.
18	9368055	Co-immunoprecipitation experiments performed on cell lysates derived from freshly isolated rat adipose cells incubated in the presence or absence of insulin indicated that twice as much phosphatidylinositol 3-kinase was associated with endogenous IRS-1 as with IRS-2 after insulin stimulation.
19	9368055	To examine the role of IRS-2 in insulin-stimulated translocation of GLUT4, we studied the effects of overexpression of IRS-1 and -2 on translocation of a co-transfected epitope-tagged GLUT4 (GLUT4-HA).
20	9388210	IGFBP-7 blocks insulin binding to the insulin receptor and thereby inhibiting the earliest steps in insulin action, such as autophosphorylation of the insulin receptor beta subunit and phosphorylation of IRS-1, indicating that IGFBP-7 is a functional insulin-binding protein.
21	9398740	This observation led to the hypothesis that these amino acid substitutions may impair the function of IRS-1, thereby causing the insulin resistance seen in patients with NIDDM.
22	9399964	This results in differential decreases in IRS-1 and IRS-2 phosphorylation, docking of the p85alpha regulatory subunit of PI 3-kinase, and activation of this enzyme in these two insulin target tissues.
23	9399964	Thus, there are multiple alterations in the early steps of insulin signaling in the ob/ob mouse, with differential regulation of IRS-1 and IRS-2, various PI 3-kinase regulatory isoforms, and a lack of compensation for the decrease in insulin signaling by any of the known alternative pathways at these levels.
24	9468528	Insulin-like growth factor-I (IGF-I) receptors activate divergent signaling pathways by phosphorylating multiple cellular proteins, including insulin receptor substrate-1 (IRS-1) and the Shc proteins.
25	9844354	Insulin receptors interact at least with three cascade reactions, phosphorylating G proteins and IRS-1, that activate PLC "ras" and PI-3-K.
26	10606633	Freshly isolated islets from IRS-1 knockout mice and SV40-transformed IRS-1-deficient beta-cell lines exhibit marked insulin secretory defects in response to glucose and arginine.
27	10606633	Furthermore, insulin expression is reduced by about 2-fold in the IRS-1-null islets and beta-cell lines, and this defect can be partially restored by transfecting the cells with IRS-1.
28	10606633	These data provide evidence for an important role of IRS-1 in islet function and provide a novel functional link between the insulin signaling and insulin secretion pathways.
29	10430617	Carriers of the Arg(972) substitution are characterized by lower fasting insulin and C-peptide levels compared with non-carriers, suggesting that the Arg(972) IRS-1 variant may contribute to impairment of insulin secretion.
30	10430617	In this study, we stably overexpressed both wild-type IRS-1 (RIN-WT) and Arg(972) IRS-1 variant (RIN-Arg(972)) in RIN beta cells to investigate directly whether the polymorphism in codon 972 of IRS-1 impairs insulin secretion.
31	10430617	The Arg(972) IRS-1 variant did not alter the extent of either glucose- or insulin-stimulated tyrosine phosphorylation of recombinant IRS-1.
32	10430617	By contrast, RIN cells expressing Arg(972) IRS-1 exhibited a marked decrease in both glucose- and sulfonylurea-stimulated insulin secretion compared with RIN-WT.
33	10811851	Expression of an IRS-1 mutant (IRS-1Deltap85) lacking the binding site for the p85 subunit of phosphatidylinositol 3-kinase (PI3K) also restored insulin sensitivity, although PI3K is known to play a crucial role in insulin's metabolic responses.
34	11147790	In this study, we have investigated the early events in the insulin pathway that trigger the degradation of IRS-1.
35	11147790	Incubation of the adipocytes with insulin induced a fast electrophoretic mobility shift of IRS-1 and a subsequent degradation of the protein.
36	11147790	Treatment of the cells with the tyrosine phosphatase inhibitor orthovanadate in the presence of insulin or okadaic acid partially inhibited the degradation of IRS-1.
37	11147790	Thus, regulation of serine/threonine versus tyrosine phosphorylation may modulate IRS-1 degradation, affecting insulin sensitivity.
38	11289048	TLK16998 alone had no effect on IR signaling in mouse 3T3-L1 adipocytes but, at concentrations as low as 3.2 micromol/l, enhanced the effects of insulin on the phosphorylation of the IR beta-subunit and IR substrate 1, and on the amount of phosphatidylinositol 3-kinase that coimmunoprecipitated with IRS-1.
39	11342531	SOCS-1 and SOCS-6 do not inhibit insulin-dependent IR autophosphorylation, but both proteins inhibit insulin-dependent activation of ERK1/2 and protein kinase B in vivo and IR-directed phosphorylation of IRS-1 in vitro.
40	11526109	Mutations of phosphoinositide-binding sites in both the pleckstrin homology and phosphotyrosine-binding domains significantly reduced the ability of Myc-tagged IRS-1 to translocate to the plasma membrane following insulin stimulation.
41	11606564	One serine residue located near the phosphotyrosine-binding (PTB) domain in IRS-1 (Ser(307) in rat IRS-1 or Ser(312) in human IRS-1) is phosphorylated via several mechanisms, including insulin-stimulated kinases or stress-activated kinases like JNK1.
42	11606564	These results suggest that inhibition of PTB domain function in IRS-1 by phosphorylation of Ser(307) (Ser(312) in human IRS-1) might be a general mechanism to regulate insulin signaling.
43	11739098	After insulin injection, pY of the IR was not different between groups, whereas pY of IRS-1 and IRS-2 was reduced (P < 0.05) in HSD vs.
44	12006586	Taken together, these data strongly suggest that unknown serine kinase activity and Ser(789) phosphorylation of IRS-1 may play an important role in attenuating insulin signaling in insulin-resistant animal models.
45	12138086	Both insulin and EGF increase the tyrosine phosphorylation and activation of IRS-1 and IRS-2, whereas EGF is also capable of activating additional PI 3-kinase pools and, thus, can augment the downstream signaling of insulin in insulin-resistant states like Type 2 diabetes.
46	12510059	An additional mechanism for modulating insulin signaling is via the down-regulation of IRS-1 protein levels.
47	12510059	Insulin-induced degradation of IRS-1 has been well documented, both in cells as well as in patients with diabetes.
48	12510059	In the present study we have examined the potential role of different signaling cascades in the insulin-induced degradation of IRS-1.
49	12510059	Second, knockout cells lacking one of the key effectors of this cascade, the phosphoinositide-dependent kinase-1, were found to be deficient in the insulin-stimulated degradation of IRS-1.
50	12510059	Third, concurrent with the decrease in IRS-1 degradation, the inhibitors of the phosphatidylinositol 3-kinase and mammalian target of rapamycin also blocked the insulin-stimulated increase in Ser(312) phosphorylation.
51	12510059	Finally, an inhibitor of c-Jun N-terminal kinase, SP600125, at 10 microm did not block IRS-1 degradation and IRS-1 Ser(312) phosphorylation yet completely blocked insulin-stimulated c-Jun phosphorylation.
52	12510059	In summary, our results indicate that the insulin-stimulated degradation of IRS-1 via the phosphatidylinositol 3-kinase pathway is in part dependent upon the Ser(312) phosphorylation of IRS-1.
53	12560330	Ectopically expressed SOCS-3 associated with the IR and suppressed insulin-dependent receptor autophosphorylation, insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, association of IRS-1 with the p85 subunit of phosphatidylinositol 3-kinase, and activation of Akt.
54	12679424	As expected, in control cells transfected with wild-type IRS-1, insulin stimulation caused an increase in p85 coimmunoprecipitated with IRS-1 as well as a 10-fold increase in IRS-1-associated PI 3-kinase activity.
55	12679424	Interestingly, when cells transfected with IRS1-T608R were stimulated with insulin, both the amount of p85 coimmunoprecipitated with IRS1-T608R as well as the associated PI 3-kinase activity were approximately 50% less than those observed with wild-type IRS-1.
56	12594228	Co-treatment of cells with insulin and LY294002, while reducing total IRS-1 phosphorylation, increased its phosphotyrosine content, enhancing IRS-1/PI3K association.
57	12594228	Suppression of IRS-1/2 down-regulation by LY294002 rescued the responsiveness of PKB and MAPK toward acute insulin stimulation.
58	12594228	IRS-2 appears to be the chief molecule responsible for MAPK and PKB activation by insulin, as knockdown of IRS-2 (but not IRS-1) by RNA interference severely impaired activation of both kinases.
59	12775712	Thus, unlike other cells, insulin can regulate VEGF expression by both IRS-1/PI 3-kinase-Akt cascade and Ras-MAPK pathways in aortic smooth muscle cells.
60	12941762	The lack of IRS-2 did not result in enhanced IRS-1 tyrosine phosphorylation or IRS-1-associated phosphatidylinositol (PI) 3-kinase activity on insulin stimulation.
61	12952969	These results show that IL-6, through effects on gene transcription, is capable of impairing insulin signaling and action but, in contrast to TNF-alpha, IL-6 does not increase pS-307 (or pS-612) of IRS-1.
62	12970360	Insulin-stimulated association of PI3K with IRS-1 and IRS-2, and PI3K activity were reduced by HGA in parallel with the changes in IRS tyrosine phosphorylation, while Grb2-IRS association was unchanged.
63	15127200	Oxidative stress induces insulin resistance by impairing IRS-1 phosphorylation and PI 3-kinase activation in the LDM fraction, and NF-kappa B activation is likely to be involved in this process.
64	15153564	As expected, phosphatidylinositol 3 kinase activity (PI3K) was suppressed in muscle; in addition to decreased insulin, the mechanism includes IRS-1 phosphorylation at serine-307.
65	15574412	This effect was stronger in the double mutant S332A/336A(IRS-1) and led to enhanced insulin-mediated activation of protein kinase B.
66	15574412	In summary, our studies identify Ser332 as the GSK-3 phosphorylation target in IRS-1, indicating its physiological relevance and demonstrating its novel inhibitory role in insulin signaling.
67	15590636	Taken together, these data indicate that the G972R naturally occurring polymorphism of IRS-1 not only reduces phosphorylation of the substrate but allows IRS-1 to act as an inhibitor of the insulin receptor kinase, producing global insulin resistance.
68	15613682	Nevertheless, there are intrinsic abnormalities in glucose transport and insulin signaling in myotubes from affected women, including increased phosphorylation of IRS-1 Ser312, that may confer increased susceptibility to insulin resistance-inducing factors in the in vivo environment.
69	15950750	Pretreatment of BMC for 10 min leptin, followed by insulin time-course, caused IRS-1 recruitment to be unresponsive, but evoked a rapid, phasic response of PI 3-kinase recruitment to the IR and abrogated the response of GLUT4 translocation to the plasma membrane evoked by insulin alone.
70	15998259	Increased serine phosphorylation of IRS reduces its ability to undergo tyrosine phosphorylation and may accelerate the degradation of IRS-1, offering an attractive explanation for the molecular basis of oxidative stress-induced insulin resistance.
71	16098829	Accumulating evidence indicates an important role for serine phosphorylation of IRS-1 in the regulation of insulin action.
72	16098829	Mass spectrometry analysis identifies IRS-1 Ser632/635 as substrates of ROK in vitro, and mutation of these sites inhibits insulin signaling.
73	16128672	Similarly, transient induction of IRS1 (3-fold) in the liver or muscle of rodents occurs following feeding or insulin injection respectively.
74	16128672	Elucidation of the mechanism by which insulin promotes IRS1 stability will permit characterization of the importance of this novel signalling event in insulin regulation of liver and muscle function.
75	16150913	In muscle from rats fed high n-6 polyunsaturated or saturated fat diets, however, there was no insulin-stimulated increase in IRS-1 Tyr612 phosphorylation and a temporal difference in PKB Ser473 phosphorylation despite no difference in IR Tyr1162/1163 phosphorylation, IRS-1 Tyr895 phosphorylation, and ERK phosphorylation.
76	16150913	These results demonstrate that under conditions of increased insulin, similar to those used to assess insulin action in vivo, chronic high-fat feeding impairs insulin signal transduction related to glucose metabolism at the level of IRS-1 Tyr612 and PKB Ser473 and that these effects are independent of the type of fat used in the high-fat diet.
77	16179348	Troglitazone increased skeletal muscle Irs-1 and phospho-Akt levels following in vivo insulin treatment, whereas AGN194204 increased hepatic Irs-2 and insulin stimulated phospho-Akt in liver.
78	16311104	After a short-term insulin stimulation (10 nmol/L insulin for 10 minutes), IR and IRS1 tyrosine phosphorylation, PI3K activation, and Akt-Ser473 phosphorylation significantly increased (P < .01 and P < .05 for Akt) in SkMC-L but not in SkMC-H.
79	16311104	Moreover, in the SkMC-H, insulin stimulation was associated with the inhibition of IRS1 tyrosine dephosphorylation (P < .05).
80	16311104	In summary, continuous exposure of cultured myoblasts to high insulin levels induces a persistent up-regulation of IR, IRS1, and PI3K activity associated with the demodulation of insulin signaling.
81	16505244	Insulin increased phosphorylation of IRS-1 at Ser (312) but not Ser (616) in healthy subjects, with impairments noted in nondiabetic kidney and pancreas-kidney transplant recipients.
82	16505244	In conclusion, peripheral insulin resistance in pancreas-kidney transplant recipients may arise from a negative feedback regulation of the canonical insulin-signaling cascade from excessive serine phosphorylation of IRS-1, possibly as a consequence of immunosuppressive therapy and hyperinsulinemia.
83	16873706	A number of serine kinases that phosphorylate serine residues of IRS-1 and weaken insulin signal transduction have been identified.
84	17003331	In contrast, insulin-stimulated extracellular signal-regulated kinase1/2 and Jun NH2-terminal kinase (JNK) activation were decreased in the presence of bradykinin, accompanied by decreased IRS-1 Ser307 phosphorylation.
85	17003331	These data indicate that bradykinin enhances insulin sensitivity in adipocytes via an NO-dependent pathway that acts by modulating the feedback inhibition of insulin signaling at the level of IRS-1.
86	17038556	By targeting IRS-1, IL-1beta is capable of impairing insulin signaling and action, and could thus participate in concert with other cytokines, in the development of insulin resistance in adipocytes.
87	17631765	TP with insulin stimulation in normal pregnancy group was lower than that in normal nonpregnant group (0.85 +/- 0.09; P<0.01). (4) Protein expression and TP with insulin stimulation of IRS-1 was negatively related to HOMA-IR in GDM group (r=- 0.613, -0.632; P<0.01), and TP with insulin stimulation was negatively related to HOMA-IR in normal pregnancy group (r=-0.526, P<0.05).
88	17640984	Phosphorylation of some serine/threonine residues in IRS-1 dampens insulin signaling, whereas phosphorylation of other serine/threonine residues enhances insulin signaling.
89	17640984	Cells expressing the Ser(629)Ala mutation, along with increased Ser(636) phosphorylation, had decreased insulin-stimulated association of the p85 regulatory subunit of phosphatidylinositol 3'-kinase with IRS-1 and decreased phosphorylation of Akt at Ser(473).
90	17575262	When insulin-resistant adipocytes from patients with type 2 diabetes were incubated with antibodies against RBP4, insulin-induced phosphorylation of IRS1 at serine (307) was normalized and the EC50 for insulin stimulation of ERK1/2 phosphorylation was reduced.
91	17971514	The insulin-induced glucose uptake was enhanced by berberine in the absence of change in IRS-1 (Ser307/312), Akt, p70 S6, and ERK phosphorylation.
92	18202124	Insulin-stimulated IRS tyrosine phosphorylation was impaired by overepxression of PKC-zeta for IRS-1, -3, and -4 but not IRS-2.
93	18202124	In cells overexpressing PKC-zeta there was marked inhibition of insulin-stimulated PI3K activity associated with IRS-1, -3 and -4 but not IRS-2.
94	18408913	In 30-week-old C57BL/6 and JYD mice, the basal levels of IRS-1, Akt and peroxisome proliferator-activated receptor-gamma decreased, as did insulin-stimulated phosphorylation of Akt and insulin receptor beta.
95	18434357	These data indicate that acute, physiological elevation in FFA has a greater impact on insulin signalling downstream of IR and IRS-1, at the level of PKB and GSK-3beta, and that under these conditions stress signalling pathways are not significantly stimulated.
96	18496818	We found that the high glucose condition causes significant increasing Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1), leading to reduce insulin-stimulated phosphorylation of Akt.
97	18496818	However, the treatment of EGCG improves insulin-stimulated downsignaling by reducing IRS-1 Ser307 phosphorylation.
98	18496818	Together, our data suggest a putative link between high glucose and insulin resistance in HepG2 cells, and the EGCG treatment attenuates insulin signaling blockade by reducing IRS-1 Ser307 phosphorylation through the AMPK activation pathway.
99	18657616	The combined therapy had a synergic effect on insulin sensitivity when their plasma levels were low (day 6) or high (day 16), that could be associated with Glut-4 plasma membrane content modulation, p85alpha-IRS-1 association and IRS-1 amount.
100	18792873	Our present study suggests that PEDF could improve the AGE-elicited insulin resistance in Hep3B cells by inhibiting JNK- and IkappaB kinase-dependent serine phosphorylation of IRS-1 via suppression of Rac-1 activation.
101	19011670	Although ramipril also reversed high blood pressure, it had a lesser effect on insulin resistance (including IRS-1) and blocked superoxide anion production only in aorta.
102	19276091	Insulin-stimulated phosphatidylinositol 3-kinase activity associated with IRS-1 or phospho-tyrosine was also reduced approximately 40% without any alteration in tyrosine phosphorylation of insulin receptor in skeletal muscle.
103	19357831	In liver, as well as in muscle, IRS-2/PI3K activation by insulin was intact, whereas IRS-1/PI3K activation by insulin was impaired.
104	19699714	In conclusion, these results suggest that Rg3 improves insulin signaling and glucose uptake primarily by stimulating the expression of IRS-1 and GLUT4.
105	19734900	Unlike previously reported T2D risk loci, which predominantly associate with impaired beta cell function, the C allele of rs2943641 was associated with insulin resistance and hyperinsulinemia in 14,358 French, Danish and Finnish participants from population-based cohorts; this allele was also associated with reduced basal levels of IRS1 protein and decreased insulin induction of IRS1-associated phosphatidylinositol-3-OH kinase activity in human skeletal muscle biopsies.
106	19675138	Prereceptor facilitation of glucocorticoid action via 11beta-HSD1 increases pSer(307) IRS1 and may be crucial in mediating insulin resistance in skeletal muscle.
107	19966489	In the BEC-treated diabetic animals, insulin induced a significant increase in plasma membrane GLUT4 and cytosolic tyrosine-phosphorylated IRS-1, indicating that it attenuates insulin resistance.
108	19716569	Diverse single nucleotide polymorphisms (SNPs) of the IRS1 gene have been associated with insulin resistance and T2D risk.
109	20569275	Upon this genetic modification, increased serine phosphorylation in Irs1 was observed and followed by impaired (3)H-deoxy-glucose uptake and muscle glycogen content, and transgenic mice exhibited insulin and glucose intolerance as they age.
110	19781106	Assessment of skeletal muscle insulin signaling demonstrated increased tyrosine phosphorylation of IRS-1 (p < 0.001) and increased IRS-1-associated phosphatidylinositol 3 (PI 3)-kinase activity (p < 0.001) following HC overfeeding.
111	19775880	Our results indicate that daidzein enhances insulin-stimulated glucose uptake in adipocytes by increasing the expression of GLUT4 and IRS-1 via the activation of PPARgamma.
112	20979575	In conclusion, obesity alone or obesity associated with Type 2 diabetes alters human periumbilical adipose tissue arterioles in terms of structure, function and biochemsitry, including diminished eNOS expression and reduced levels of IRS-1, IRS-2, PI3K and Akt in the insulin signalling pathway.
113	21134353	In conclusion, CR reduced ER stress and improved hepatic insulin action by suppressing JNK-mediated IRS-1 serine-phosphorylation in ob/ob mice.
114	20028942	By regulating the phosphorylation state of IR, PTB1B determines sensitivity to insulin in liver and exerts a unique role in the interplay between IRS1 and IRS2 in the modulation of hepatic insulin action.
115	21472564	Defects in the protein-protein interactions involving IRS-1 may lead to the development of insulin resistance and type 2 diabetes.
116	20466847	Genetic and biological studies have shown that reductions in IRS1 and/or IRS2 protein levels are associated with insulin resistance.
117	20466847	In contrast to the insulin-induced degradation of IRS1, HG-induced degradation of IRS1 did not require IR signaling or phosphatidylinositol 3-kinase/Akt activity.
118	21088934	To investigate insulin sensitivity within the liver, serine phosphorylation of IRS-1 (Ser307) and Akt (Ser473) and expression of gluconeogenic genes, PEPCK and G6Pase, were tested.
119	21589939	IRS-1 serine phosphorylation was increased (1.30�0.09 vs. 0.22�0.03 OD units, P<0.005) while insulin-stimulated tyrosine phosphorylation decreased (10.97�0.95 vs. 0.89�0.50 OD units, P<0.005).
120	21731668	After 8 weeks on HFD, mice developed obesity, fatty liver, inflammatory changes in adipose tissue and insulin resistance at the level of IRS-1 phosphorylation, as well as alterations in metabolomic profile of amino acid metabolites, TCA cycle intermediates, glucose and cholesterol metabolites, and fatty acids in liver, muscle, fat and serum.
121	11862322	In conclusion, the Arg972 (IRS-1) background produced a marked difference in insulin sensitivity between X/Ala and Pro/Pro (PPARgamma) which was not present in the whole population or against the Gly972 (IRS-1) background.
122	18952837	Skeletal muscle triglyceride was 38% lower, and insulin-stimulated phosphorylated Akt (Ser473) was twofold greater in SMLPL(-/-) mice without changes in IRS-1 tyrosine phosphorylation and phosphatidylinositol 3-kinase activity.
123	21296137	PA-evoked inflammation impaired insulin signaling cascades and mSMS improved insulin signaling transduction by modification of Ser/Thr phosphorylation of IRS-1 and downstream Akt (T308), thereby improved insulin sensitivity in hepatocytes. mSMS also improved glucose intolerance induced by inflammatory cytokines in normoglycemic mice, which further demonstrated its modulation toward insulin sensitivity in vivo.
124	21799686	EA stimulated the expression of IRS1 and AKT2 and atropine treatment blocked the EA-induced expression of those insulin signaling proteins.
125	21647634	In conclusion, (i) STEAP4 regulates the function of IRS-1, PI3K, and Akt and decreases insulin-induced GLUT4 translocation and glucose uptake; (ii) ROS-related mitochondrial dysfunction may be related to a reduced IRS-1 correlation with the PI3K signaling pathway, leading to insulin resistance.
126	21602124	APN may decrease tyrosin phosphorylation of IRS-1 via the IKK/NF?B pathway and inhibit insulin signaling pathway in the liver, which contributes to hyerlipidemia, hyperglycemia and development of type 2 diabetes.
127	21850561	We used HPLC-electrospray ionisation (ESI)-MS/MS to quantify IRS-1 phosphorylation basally and after insulin infusion in vastus lateralis muscle from lean healthy, obese non-diabetic and type 2 diabetic volunteers.
128	21850561	Insulin increased IRS-1 phosphorylation at Ser527 (1.4?�?0.17, p???0.01, fold change, 60 min after insulin infusion vs basal) and Ser531 (1.3?�?0.16, p???0.01, fold change, 60 min after insulin infusion vs basal) in the lean controls and suppressed phosphorylation at Ser348 (0.56?�?0.11, p???0.01, fold change, 240 min after insulin infusion vs basal), Thr446 (0.64?�?0.16, p???0.05, fold change, 60 min after insulin infusion vs basal), Ser1100 (0.77?�?0.22, p???0.05, fold change, 240 min after insulin infusion vs basal) and Ser1142 (1.3?�?0.2, p???0.05, fold change, 60 min after insulin infusion vs basal).
129	21850561	However, some IRS-1 phosphorylation sites do not respond to insulin, whereas other Ser/Thr phosphorylation sites are either increased or decreased in insulin resistance.
130	21803028	In corresponding Ang-IV treated animals, insulin induced IRAP and PI3K interaction, activation of pAkt and GLUT4 translocation, but no corresponding activation of IR, IRS-1 and IRS-1-PI3K coupling were observed.
131	22001674	These findings suggest that improvements in glucose tolerance and insulin resistance following RYGB surgery are associated with upregulation of IRS-1.
132	10077007	Overexpression of IRS-1 led to a 2-fold increase in cell surface GLUT4-HA in cells incubated in the absence of insulin; overexpression of either IRS-3 or IRS-4 elicited a larger increase in cell surface GLUT4-HA.
133	11641236	In fact, IRS-1 appears to have its major role in skeletal muscle whereas IRS-2 appears to regulate hepatic insulin action as well as pancreatic beta cell development and survival.
134	14623899	Replacing Ser(302) with alanine significantly reduced insulin-stimulated tyrosine phosphorylation of IRS-1 and p85 binding and reduced insulin-stimulated phosphorylation of p70(S6K), ribosomal S6 protein, and 4E-BP1; however, this mutation had no effect on insulin-stimulated Akt or glycogen synthase kinase 3beta phosphorylation.
135	16960890	TNF-alpha pre-incubation also showed reduced insulin-stimulated Tyr phosphorylation of insulin receptor (IR-beta) in both the cell types, moreover hyperphosphorylation of IRS-1 at Ser 312 residue was observed in TNF-alpha pre-incubated cells.
136	16960890	As hyperphosphorylation of IRS-1 at Ser 312 can induce its degradation, it is possible that reduced insulin responsiveness after long-term TNF-alpha pre-incubation observed in this study is due to the decrease in IRS-1 levels.
137	17021050	These data indicate distinct roles for Akt-1 and Akt-2 in muscle glucose metabolism and that moderate reductions in IRS-1 expression do not result in the development of insulin resistance in skeletal muscle in vivo.